2. Academic Validation
  3. Programmed NP Cell Death Induced by Mitochondrial ROS in a One-Strike Loading Disc Degeneration Organ Culture Model

Programmed NP Cell Death Induced by Mitochondrial ROS in a One-Strike Loading Disc Degeneration Organ Culture Model

  • Oxid Med Cell Longev. 2021 Aug 31:2021:5608133. doi: 10.1155/2021/5608133.
Bao-Liang Li 1 2,  Xizhe Liu 2,  Manman Gao 3 4,  Fu Zhang 1,  Xu Chen 1,  Zhongyuan He 1,  Jianmin Wang 1,  Wei Tian 5,  Dafu Chen 5,  Zhiyu Zhou 1 2,  Shaoyu Liu 1 2
Affiliations

Affiliations

  • 1 Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
  • 2 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute/Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
  • 3 Department of Sport Medicine, Inst Translat Med, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518000, China.
  • 4 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, China.
  • 5 Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing Jishuitan Hospital, Beijing 100035, China.
PMID: 34512867 DOI: 10.1155/2021/5608133
Abstract

Increasing evidence has indicated that mitochondrial Reactive Oxygen Species (ROS) play critical roles in mechanical stress-induced lumbar degenerative disc disease (DDD). However, the detailed underlying pathological mechanism needs further investigation. In this study, we utilized a one-strike loading disc degeneration organ culture model to explore the responses of intervertebral discs (IVDs) to mechanical stress. IVDs were subjected to a strain of 40% of the disc height for one second and then cultured under physiological loading. Mitoquinone mesylate (MitoQ) or Other inhibitors were injected into the IVDs. IVDs subjected to only physiological loading culture were used as controls. Mitochondrial membrane potential was significantly depressed immediately after mechanical stress (P < 0.01). The percentage of ROS-positive cells significantly increased in the first 12 hours after mechanical stress and then declined to a low level by 48 hours. Pretreatment with MitoQ or rotenone significantly decreased the proportion of ROS-positive cells (P < 0.01). Nucleus pulposus (NP) cell viability was sharply reduced at 12 hours after mechanical stress and reached a stable status by 48 hours. While the levels of necroptosis- and apoptosis-related markers were significantly increased at 12 hours after mechanical stress, no significant changes were observed at day 7. Pretreatment with MitoQ increased NP cell viability and alleviated the marker changes by 12 hours after mechanical stress. Elevated mitochondrial ROS levels were also related to extracellular matrix (ECM) degeneration signs, including catabolic marker upregulation, anabolic marker downregulation, increased glycosaminoglycan (GAG) loss, IVD dynamic compressive stiffness reduction, and morphological degradation changes at the early time points after mechanical stress. Pretreatment with MitoQ alleviated some of these degenerative changes by 12 hours after mechanical stress. These changes were eliminated by day 7. Taken together, our findings demonstrate that mitochondrial ROS act as important regulators of programmed NP cell death and ECM degeneration in IVDs at early time points after mechanical stress.

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